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Studies of the p53 gene in thyroid carcinoma


, : Studies of the p53 gene in thyroid carcinoma. Medical Journal of Kinki University 19(4): 483-498

There is a wide variety of thyroid tumor varying from slowly growing differentiated adenocarcinoma to rapidly proliferating undifferentiated carcinoma. In this study, 33 human thyroid carcinomas (17 papillary carcinomas, 6 follicular carcinomas, 1 medullary carcinoma, 9 undifferentiated carcinomas) were examined for the mutation or rearrangement of the p53 gene using DNA obtained from snap-frozen or paraffin-embedded cancer materials. The mutation was studied for exons 5-8 of the p53 gene by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis using silver staining. The thyroid tumors showing mobility different from that of normal thyroid tissues obtained by this method, were further investigated by the nonradioisotopic direct cycle sequence method. Mutations were found in 8 of 9 undifferentiated carcinomas and 1 of 23 differentiated carcinomas. For undifferentiated carcinoma, 4 out of 8 patients with positive mutations showed the A:T to T:A transversion and most mutations were located in exons 6 and 7. Two undifferentiated carcinomas showed a mutation from TGC to GC (Cys to Ser) in codon 242. Southern blot analysis of DNA preparations obtained from 19 differentiated thyroid carcinomas and 19 normal thyroid tissues as the control was performed using restriction enzymes including Eco RI, Bam HI and Pvu II as well as a p53 cDNA probe (1.3 kb). Neither rearrangement nor deletion was detected for 19 differentiated thyroid carcinomas. These findings suggest that the p53 mutation exists in a high frequency in undifferentiated thyroid carcinoma but is rare in well-differentiated thyroid adenocarcinoma.

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